We plan to study whether CCl4 activation to CCl3 free radicals and lipid peroxidation occurs at the rat and mouse liver nuclear envelope. Experiments are going to be performed to detect possible covalent binding of CCl3 to either/ and/or the heme and apoprotein portion of cytochrome P-450. Studies are going to be performed to understand if covalent binding of CCl4 metabolites or lipid peroxidation is responsible for dilatation of the endoplasmic reticulum and for polysome detachment from rough endoplasmic reticulum membranes and for their rupture as well as to damage to plasma membrane. We are going to study further the binding of CCl3 to liver DNA nucleic acid bases and we also plan to explore if CHCl3 which is a CCl4 metabolite binds to DNA, RNA and nuclear proteins because these studies might be relevant to carcinogenic effects of both haloalkanes. Studies by electron microscopy and by biochemical procedures are going to be performed to shed light into the process of cell death induction by hepatotoxines particularly to the role played by protein synthesis and protein degradation as well as covalent binding in it. We plan to continue our studies on substances that we found to stop cell death induced by several hepatotoxic compounds as well as their suitability for therapeutic treatments.